I ordered an 8 a.m. cortisol and ACTH (adrenocorticotropic hormone) draw; should I wait for the results before sending the levothyroxine prescription to the pharmacy, or can I send it now?

Wait for Cortisol and ACTH Results Before Sending Levothyroxine

You must wait for the 8 a.m. cortisol and ACTH results before initiating levothyroxine, because starting thyroid hormone in a patient with undiagnosed adrenal insufficiency can precipitate a life-threatening adrenal crisis. 1

Why This Matters: The Physiological Mechanism

When you give levothyroxine to someone with untreated adrenal insufficiency, the thyroid hormone accelerates cortisol metabolism and increases the body's metabolic demands—essentially unmasking or worsening the cortisol deficit 1. This can trigger acute adrenal crisis with hypotension, shock, and cardiovascular collapse 1, 2, 3.

In patients with concurrent hypothyroidism and adrenal insufficiency, corticosteroids must always be started several days before thyroid hormone replacement to prevent precipitating adrenal crisis 1.

The Clinical Scenario You're Evaluating

You ordered morning cortisol and ACTH for a reason—presumably because:

• The patient has clinical features that raise concern for adrenal insufficiency (hypotension, hyponatremia, unexplained symptoms, or autoimmune disease history) 1
• You're evaluating for possible polyglandular autoimmune syndrome, where primary hypothyroidism and primary adrenal insufficiency frequently coexist 4, 2, 3
• The patient has suspected central hypothyroidism or hypophysitis, where multiple pituitary hormone deficiencies can occur together 1, 5

Diagnostic Thresholds for Adrenal Insufficiency

Once you have the results:

• Basal cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH in acute illness is diagnostic of primary adrenal insufficiency 1
• Basal cortisol <400 nmol/L (<14.5 μg/dL) with elevated ACTH raises strong suspicion and warrants cosyntropin stimulation testing 1
• Low or inappropriately normal ACTH with low cortisol suggests secondary adrenal insufficiency 1

If the cosyntropin stimulation test is needed, a peak cortisol <500 nmol/L (<18 μg/dL) at 30 or 60 minutes confirms adrenal insufficiency 1.

Management Algorithm Based on Results

If Adrenal Insufficiency Is Confirmed or Strongly Suspected:

1. Start hydrocortisone 20 mg in the morning and 10 mg in the afternoon (or equivalent stress-dose corticosteroids) immediately 1, 5
2. Wait at least one week before initiating levothyroxine 1, 5
3. Add fludrocortisone 0.05–0.1 mg daily if primary adrenal insufficiency is confirmed 1
4. Only after corticosteroid coverage is established, begin levothyroxine at an appropriate dose 1, 5

If Adrenal Insufficiency Is Ruled Out:

• Proceed with levothyroxine initiation based on standard hypothyroidism treatment guidelines 5
• For patients <70 years without cardiac disease, start at approximately 1.6 mcg/kg/day 5, 6
• For patients >70 years or with cardiac disease, start at 25–50 mcg/day and titrate gradually 5

Real-World Case Examples Illustrating This Risk

Case 1: A 21-year-old man presented with lethargy, hypotension, hyponatremia, and elevated TSH. He was started on levothyroxine for presumed hypothyroidism but showed no response. Workup later revealed primary adrenal insufficiency. All symptoms resolved only after starting hydrocortisone, fludrocortisone, and then continuing levothyroxine 2.

Case 2: A 46-year-old woman with "treatment-resistant hypothyroidism" had progressive fatigue and dizziness. When liothyronine (T3) was added, her symptoms worsened dramatically. Morning cortisol was low with failure to respond to cosyntropin stimulation, confirming primary adrenal insufficiency. She required hydrocortisone before thyroid hormone could be safely continued 3.

Case 3: A 50-year-old man had simultaneous primary hypothyroidism (elevated TSH, positive anti-thyroid antibodies) and isolated ACTH deficiency causing secondary adrenal insufficiency. Treatment required cortisol replacement before thyroid hormone to prevent crisis 4.

Common Pitfalls to Avoid

• Never assume normal electrolytes rule out adrenal insufficiency—hyperkalemia is present in only ~50% of primary adrenal insufficiency cases, and hyponatremia can occur in both adrenal insufficiency and hypothyroidism 1
• Don't start levothyroxine based on elevated TSH alone without considering the full clinical picture, especially if the patient has unexplained hypotension, hyponatremia, or autoimmune disease 1, 2, 3
• Recognize that "treatment-resistant hypothyroidism" may actually be undiagnosed adrenal insufficiency—if symptoms worsen or fail to improve with levothyroxine, immediately evaluate adrenal function 2, 3

The Bottom Line

Wait for the 8 a.m. cortisol and ACTH results. If they suggest adrenal insufficiency, start corticosteroids first and delay levothyroxine for at least one week 1, 5. If adrenal function is normal, proceed with levothyroxine 5. This approach prevents a potentially fatal adrenal crisis and ensures safe, effective treatment of hypothyroidism 1, 2, 3.